Building and establishing platform technologies for Structure Based Drug Design targeting AdipoR
| Project/Area Number |
26293216
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Iwabu Miki 東京大学, 医学部附属病院, 特任講師 (70392529)
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| Co-Investigator(Renkei-kenkyūsha) |
IWABU Masato 東京大学, 医学部附属病院, 特任准教授 (30557236)
YAMAUCHI Toshimasa 東京大学, 医学部附属病院, 准教授 (40372370)
KADOWAKI Takashi 東京大学, 医学部附属病院, 教授 (30185889)
TOKOYAMA Shigeyuki 独立行政法人理化学研究所, 横山構造生物学研究室, 上席研究員 (00159229)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
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| Keywords | 糖尿病 / 薬理学 / トランスレーショナルリサーチ |
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| Outline of Final Research Achievements |
We have so far clarified that adiponectin, an adipocyte-secreted physiologically active substance, is decreased with the onset of obesity and that lifestyle-related diseases are primarily accounted for by the systemically decreased action of adiponectin/adiponectin receptors (AdipoRs). We were the first in the world to succeed in identifying small-molecule compounds that serve as seed compounds for candidate AdipoR-activating drugs. In the process, we have also reported the crystal structures of AdipoRs, which allowed the seed compounds to be structurally developed, examined for their anti-diabetic properties at the cellular and organism levels, and optimized as candidate compounds for clinical development, with their activity, specificity and safety highly enhanced over those of existing small-molecule AdipoR-activating compounds. It is hoped that these milestones will lead to the development of novel anti-diabetic drugs.
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Report
(4 results)
Research Products
(42 results)
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[Journal Article] Crystal structures of the human adiponectin receptors.2015
Author(s)
Tanabe H, Fujii Y, Okada-Iwabu M, Iwabu M, Nakamura Y, Hosaka T, Motoyama K, Ikeda M, Wakiyama M, Terada T, Ohsawa N, Hato M, Ogasawara S, Hino T, Murata T, Iwata S, Hirata K, Kawano Y, Yamamoto M, Kimura-Someya T, Shirouzu M, Yamauchi T, Kadowaki T, Yokoyama S
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Journal Title
Nature
Volume: 520
Issue: 7547
Pages: 312-316
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] A Novel Peroxisome Proliferator-activated Receptor (PPAR)α Agonist and PPARγ Antagonist, Z-551, Ameliorates High-fat Diet-induced Obesity and Metabolic Disorders in Mice.2015
Author(s)
Shiomi Y, Yamauchi T, Iwabu M, Okada-Iwabu M, Nakayama R, Orikawa Y, Yoshioka Y, Tanaka K, Ueki K, Kadowaki T
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Journal Title
J Biol Chem
Volume: 290
Issue: 23
Pages: 14567-14581
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Expression, purification, crystallization, and preliminary X-ray crystallographic studies of the human adiponectin receptors, AdipoRl and AdipoR22015
Author(s)
Tanabe H,..., Iwata S, Okada-Iwabu M, Iwabu M,..., Yamauchi T, Kadowaki T, and Yokoyama S
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Journal Title
J. Struct. Funct. Genomics
Volume: 16
Issue: 1
Pages: 11-23
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Crystal structures of the human adiponectin receptors2015
Author(s)
MIKI OKADA-IWABU, TOSHIMASA YAMAUCHI, MASATO IWABU,TAKASHI KADOWAKI
Organizer
2016 Keystone Symposia Conference T2: Diabetes: New Insights into Molecular Mechanisms and Therapeutic Strategies
Place of Presentation
Westin Miyako Kyoto（京都府京都市）
Year and Date
2015-10-13
Related Report
Int'l Joint Research
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